This proposal seeks to explore the factors underlying higher morbidity in minority groups with systemic lupus erythematosus by examining the relationship of socioeconomic, demographic, cultural, immunogenetic, and clinical variables to early outcome in a study of Hispanic, African-American, and Caucasian SLE patients from 2 geographic areas: Houston, Texas and Birmingham, Alabama. Since enrollment for the study began in April, 1994, a total of 122 patients meeting criteria for SLE have been enrolled at the University Clinical Research Center at the University of Texas Health Science Center. Immunogenetic analysis of these and the additional patients seen at The University of Alabama at Birmingham and the University of Texas Medical Branch at Galveston reveals an association with HLA-DRB1*0301 in Caucasians, DRB1*1503 in African -Americans and DRB1*08 in Hispanics. Preliminary analysis of the two year followup data in 160 of the 183 patients who have completed this visit indicate both genetic, sociodemographic and behavioral factors to independently predict cumulative disease damage as well as the persistence of disease activity over time. However, the persistence of ethnicity in the models as a predictive factor in disease damage and activity is explained by the presence of other genes we have recently studied in this cohort, including TNF , IL-10 promoter genes, and BCL2. We submitted a competitive renewal, which was funded for five years beginning September 1, 1998. We are planning to enroll an additional 93 patients here at the University of Texas-Houston.